A Re-evaluation of the Optimal Liver Copper Concentrations for Health, Performance and Fertility of Replacement Holstein-Friesian Heifers.

Excessive copper (Cu) supplementation is common on dairy farms worldwide, despite a growing body of research highlighting the risks of over-supplementation, including liver damage, impaired growth, and reduced fertility. However, diagnosing Cu toxicity remains challenging due to the liver's allostatic regulation of blood Cu levels and debate surrounding toxicity thresholds. This study utilised secondary data from a longitudinal study conducted between September 2016 and September 2018 involving 80 replacement Holstein-Friesian heifers. Data was utilised to generate receiver operating characteristic curves which established liver Cu thresholds associated with suboptimal liver function and fertility. Results indicated that hepatic Cu concentrations exceeding 167 mg/kg of dry matter (DM) were associated with reduced conception rates to first service, while concentrations above 260 mg/kg of DM reduced conception probability to first and second services. Hepatic Cu concentrations exceeding 322 mg/kg of DM were linked to impaired liver function, as evidenced by elevated serum glutamate dehydrogenase activity. In contrast, a toxicity threshold value could not be generated for plasma Cu, underscoring its inadequacy as a biomarker. The fertility thresholds identified in this study may be more closely related to optimizing Cu levels for animal performance rather than indicative of liver Cu toxicity, suggesting the need for further research.